Aptamer-guided acridine derivatives for cervical cancer

Organic & Biomolecular Chemistry
Josué CarvalhoCarla Cruz

Abstract

DNA aptamers represent a way to target cancer cells at a molecular level and continue to be developed with a view to improve treatment and imaging in cancer medicine. AT11-L0, derived from the DNA sequence AT11, forms a single major parallel G-quadruplex (G4) conformation and exhibits an anti-proliferative activity similar to that of AT11 and AS1411 aptamers. On the other side, acridine orange derivatives represent a valuable class of G4 ligands. Herein, we evaluate AT11-L0 G4 as a supramolecular carrier for the delivery of acridine ligands C3, C5 and C8 to HeLa cancer cells. The CD titrations suggest no changes in the chiroptical signal upon addition of an excess of ligands maintaining the parallel G4 topology and C8 stabilizes the structure for more than 20 °C. All the ligands exhibit high affinity (micromolar range) towards AT11-L0 G4, and the respective complexes against nucleolin (nanomolar range) suggesting that the ligands do not negatively affect the recognition of the nucleolin by AT11-L0 G4. NMR studies showed that AT11-L0 forms a G4 containing four G-tetrad layers. Ligand C8 binds AT11-L0 G4 through π-π stacking of the acridine moiety onto the top-tetrad with the involvement of additional interactions with the ligand...Continue Reading

References

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Citations

Dec 22, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fadwa OdehSaid I Ismail
Jun 18, 2019·Journal of Biomolecular Structure & Dynamics·Josué CarvalhoCarla Cruz
Oct 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Carolina RoxoAnna Pasternak
Mar 8, 2021·Talanta·André MirandaCarla Cruz
Jun 3, 2021·International Journal of Molecular Sciences·Carolina RoxoAnna Pasternak
Jul 3, 2021·Pharmaceuticals·Elisa PalmaAntónio Paulo
Aug 7, 2021·Pharmaceuticals·Jéssica Lopes-NunesCarla Cruz
Oct 29, 2019·Journal of Chemical Information and Modeling·Brianda L SantiniVerónica A Jiménez

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Methods Mentioned

BETA
saturation binding
NMR
confocal microscopy
fluorescence
fluorescence titration
fluorescence spectroscopy
electrophoresis

Software Mentioned

OriginPro
Aptamera
Topspin

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